Quantitative structure-activity relationship studies of [(biphenyloxy)propyl]isoxazole derivatives. Inhibitors of human rhinovirus 2 replication

J Med Chem. 2007 Aug 23;50(17):4205-13. doi: 10.1021/jm0704806. Epub 2007 Aug 1.


The 50% cytotoxic concentration (CC50) in HeLa cells, the 50% inhibitory concentration (IC50) against human rhinovirus 2 (HRV-2), and the selectivity index (SI = CC50/IC50) of [(biphenyloxy)propyl]isoxazole derivatives were used to develop quantitative structure-activity relationships (QSAR) based on simplex representation of molecular structure. Statistic characteristics for partial least-squares models are quite satisfactory (R2 = 0.838 - 0.918; Q2 = 0.695 - 0.87) for prediction of CC50, IC50, and SI values and permit the virtual screening and molecular design of new compounds with strong anti-HRV-2 activity. The quality of prognosis for designed compounds was additionally estimated by analysis of domain applicability for each QSAR model. A hypothesis to the effect that terminal benzene substituents must have negative electrostatic potential and definite length (approximately 5.5-5.6 A) to possess strong antiviral activity has been suggested. The quality of developed analysis, i.e., high level of antiviral action of three new designed compounds, has been confirmed experimentally.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antiviral Agents / chemical synthesis*
  • Antiviral Agents / pharmacology
  • Antiviral Agents / toxicity
  • HeLa Cells
  • Humans
  • Isoxazoles / chemical synthesis*
  • Isoxazoles / pharmacology
  • Isoxazoles / toxicity
  • Least-Squares Analysis
  • Models, Molecular*
  • Molecular Structure
  • Quantitative Structure-Activity Relationship*
  • Rhinovirus / drug effects*
  • Rhinovirus / physiology
  • Virus Replication / drug effects


  • Antiviral Agents
  • Isoxazoles